diff --git a/pkgs/build-support/setup-hooks/auto-patchelf.sh b/pkgs/build-support/setup-hooks/auto-patchelf.sh
index d310f8255224f..4b3a1c5c39092 100644
--- a/pkgs/build-support/setup-hooks/auto-patchelf.sh
+++ b/pkgs/build-support/setup-hooks/auto-patchelf.sh
@@ -63,10 +63,9 @@ getRpathFromElfBinary() {
     # NOTE: This does not use runPatchelf because it may encounter non-ELF
     # files. Caller is expected to check the return code if needed.
     local rpath
-    rpath="$(patchelf --print-rpath "$1" 2> /dev/null)" || return $?
+    IFS=':' read -ra rpath < <(patchelf --print-rpath "$1" 2> /dev/null) || return $?
 
-    local IFS=':'
-    printf "%s\n" $rpath
+    printf "%s\n" "${rpath[@]}"
 }
 
 populateCacheForDep() {
@@ -115,8 +114,52 @@ populateCacheWithRecursiveDeps() {
     done
 }
 
-getSoArch() {
-    $OBJDUMP -f "$1" | sed -ne 's/^architecture: *\([^,]\+\).*/\1/p'
+getBinArch() {
+    $OBJDUMP -f "$1" 2> /dev/null | sed -ne 's/^architecture: *\([^,]\+\).*/\1/p'
+}
+
+# Returns the specific OS ABI for an ELF file in the format produced by
+# readelf(1), like "UNIX - System V" or "UNIX - GNU".
+getBinOsabi() {
+    $READELF -h "$1" 2> /dev/null | sed -ne 's/^[ \t]*OS\/ABI:[ \t]*\(.*\)/\1/p'
+}
+
+# Tests whether two OS ABIs are compatible, taking into account the generally
+# accepted compatibility of SVR4 ABI with other ABIs.
+areBinOsabisCompatible() {
+    local wanted="$1"
+    local got="$2"
+
+    if [[ -z "$wanted" || -z "$got" ]]; then
+        # One of the types couldn't be detected, so as a fallback we'll assume
+        # they're compatible.
+        return 0
+    fi
+
+    # Generally speaking, the base ABI (0x00), which is represented by
+    # readelf(1) as "UNIX - System V", indicates broad compatibility with other
+    # ABIs.
+    #
+    # TODO: This isn't always true. For example, some OSes embed ABI
+    # compatibility into SHT_NOTE sections like .note.tag and .note.ABI-tag.
+    # It would be prudent to add these to the detection logic to produce better
+    # ABI information.
+    if [[ "$wanted" == "UNIX - System V" ]]; then
+        return 0
+    fi
+
+    # Similarly here, we should be able to link against a superset of features,
+    # so even if the target has another ABI, this should be fine.
+    if [[ "$got" == "UNIX - System V" ]]; then
+        return 0
+    fi
+
+    # Otherwise, we simply return whether the ABIs are identical.
+    if [[ "$wanted" == "$got" ]]; then
+        return 0
+    fi
+
+    return 1
 }
 
 # NOTE: If you want to use this function outside of the autoPatchelf function,
@@ -127,6 +170,7 @@ getSoArch() {
 findDependency() {
     local filename="$1"
     local arch="$2"
+    local osabi="$3"
     local lib dep
 
     if [ $depCacheInitialised -eq 0 ]; then
@@ -138,7 +182,7 @@ findDependency() {
 
     for dep in "${autoPatchelfCachedDeps[@]}"; do
         if [ "$filename" = "${dep##*/}" ]; then
-            if [ "$(getSoArch "$dep")" = "$arch" ]; then
+            if [ "$(getBinArch "$dep")" = "$arch" ] && areBinOsabisCompatible "$osabi" "$(getBinOsabi "$dep")"; then
                 foundDependency="$dep"
                 return 0
             fi
@@ -162,7 +206,24 @@ autoPatchelfFile() {
     local dep rpath="" toPatch="$1"
 
     local interpreter
-    interpreter="$(< "$NIX_CC/nix-support/dynamic-linker")"
+    interpreter="$(< "$NIX_BINTOOLS/nix-support/dynamic-linker")"
+
+    local interpreterArch interpreterOsabi toPatchArch toPatchOsabi
+    interpreterArch="$(getBinArch "$interpreter")"
+    interpreterOsabi="$(getBinOsabi "$interpreter")"
+    toPatchArch="$(getBinArch "$toPatch")"
+    toPatchOsabi="$(getBinOsabi "$toPatch")"
+
+    if [ "$interpreterArch" != "$toPatchArch" ]; then
+        # Our target architecture is different than this file's architecture,
+        # so skip it.
+        echo "skipping $toPatch because its architecture ($toPatchArch) differs from target ($interpreterArch)" >&2
+        return 0
+    elif ! areBinOsabisCompatible "$interpreterOsabi" "$toPatchOsabi"; then
+        echo "skipping $toPatch because its OS ABI ($toPatchOsabi) is not compatible with target ($interpreterOsabi)" >&2
+        return 0
+    fi
+
     if isExecutable "$toPatch"; then
         runPatchelf --set-interpreter "$interpreter" "$toPatch"
         # shellcheck disable=SC2154
@@ -175,7 +236,7 @@ autoPatchelfFile() {
     fi
 
     local libcLib
-    libcLib="$(< "$NIX_CC/nix-support/orig-libc")/lib"
+    libcLib="$(< "$NIX_BINTOOLS/nix-support/orig-libc")/lib"
 
     echo "searching for dependencies of $toPatch" >&2
 
@@ -187,14 +248,21 @@ autoPatchelfFile() {
     # new package where you don't yet know its dependencies.
 
     for dep in $missing; do
-        # Check whether this library exists in libc. If so, we don't need to do
-        # any futher searching -- it will be resolved correctly by the linker.
-        if [ -f "$libcLib/$dep" ]; then
+        if [[ "$dep" == /* ]]; then
+            # This is an absolute path. If it exists, just use it. Otherwise,
+            # we probably want this to produce an error when checked (because
+            # just updating the rpath won't satisfy it).
+            if [ -f "$dep" ]; then
+                continue
+            fi
+        elif [ -f "$libcLib/$dep" ]; then
+            # This library exists in libc, and will be correctly resolved by
+            # the linker.
             continue
         fi
 
         echo -n "  $dep -> " >&2
-        if findDependency "$dep" "$(getSoArch "$toPatch")"; then
+        if findDependency "$dep" "$toPatchArch" "$toPatchOsabi"; then
             rpath="$rpath${rpath:+:}${foundDependency%/*}"
             echo "found: $foundDependency" >&2
         else
diff --git a/pkgs/top-level/all-packages.nix b/pkgs/top-level/all-packages.nix
index eb555741b36ff..d24556eb74041 100644
--- a/pkgs/top-level/all-packages.nix
+++ b/pkgs/top-level/all-packages.nix
@@ -143,7 +143,8 @@ with pkgs;
 
   autorestic = callPackage ../tools/backup/autorestic { };
 
-  autoPatchelfHook = makeSetupHook { name = "auto-patchelf-hook"; }
+  autoPatchelfHook = makeSetupHook
+    { name = "auto-patchelf-hook"; deps = [ bintools ]; }
     ../build-support/setup-hooks/auto-patchelf.sh;
 
   appimageTools = callPackage ../build-support/appimage {