diff --git a/src/cmd/go/go_test.go b/src/cmd/go/go_test.go
index 7d80d965ae..25c1846921 100644
--- a/src/cmd/go/go_test.go
+++ b/src/cmd/go/go_test.go
@@ -3614,8 +3614,8 @@ func TestBinaryOnlyPackages(t *testing.T) {
 	tg.grepStdout("false", "did not see BinaryOnly=false for p4")
 }
 
-// Issue 16050.
-func TestAlwaysLinkSysoFiles(t *testing.T) {
+// Issue 16050 and 21884.
+func TestLinkSysoFiles(t *testing.T) {
 	tg := testgo(t)
 	defer tg.cleanup()
 	tg.parallel()
@@ -3634,6 +3634,10 @@ func TestAlwaysLinkSysoFiles(t *testing.T) {
 	tg.setenv("CGO_ENABLED", "0")
 	tg.run("list", "-f", "{{.SysoFiles}}", "syso")
 	tg.grepStdout("a.syso", "missing syso file with CGO_ENABLED=0")
+
+	tg.setenv("CGO_ENABLED", "1")
+	tg.run("list", "-msan", "-f", "{{.SysoFiles}}", "syso")
+	tg.grepStdoutNot("a.syso", "unexpected syso file with -msan")
 }
 
 // Issue 16120.
diff --git a/src/cmd/go/internal/load/pkg.go b/src/cmd/go/internal/load/pkg.go
index 60de666164..4fbde1de8c 100644
--- a/src/cmd/go/internal/load/pkg.go
+++ b/src/cmd/go/internal/load/pkg.go
@@ -207,6 +207,12 @@ func (p *Package) copyBuild(pp *build.Package) {
 	p.SwigFiles = pp.SwigFiles
 	p.SwigCXXFiles = pp.SwigCXXFiles
 	p.SysoFiles = pp.SysoFiles
+	if cfg.BuildMSan {
+		// There's no way for .syso files to be built both with and without
+		// support for memory sanitizer. Assume they are built without,
+		// and drop them.
+		p.SysoFiles = nil
+	}
 	p.CgoCFLAGS = pp.CgoCFLAGS
 	p.CgoCPPFLAGS = pp.CgoCPPFLAGS
 	p.CgoCXXFLAGS = pp.CgoCXXFLAGS