diff --git a/crates/guest-rust/build.rs b/crates/guest-rust/build.rs
index 0793c250d..b7f0f94c5 100644
--- a/crates/guest-rust/build.rs
+++ b/crates/guest-rust/build.rs
@@ -1,7 +1,17 @@
 use std::env;
 use std::path::PathBuf;
+use std::process::Command;
 
 fn main() {
+    println!("cargo:rustc-check-cfg=cfg(wasi_has_initialize)");
+
+    let target_os = env::var("CARGO_CFG_TARGET_OS").unwrap_or_default();
+    // Rust 1.100 supplies `_initialize` for WASI cdylibs:
+    // https://github.com/rust-lang/rust/pull/161421
+    // Remove the version check once the MSRV reaches 1.100.
+    if target_os == "wasi" && rustc_minor_version().unwrap_or(0) >= 100 {
+        println!("cargo:rustc-cfg=wasi_has_initialize");
+    }
     let target_arch = env::var("CARGO_CFG_TARGET_ARCH").unwrap_or(String::new());
     let target_family = env::var("CARGO_CFG_TARGET_FAMILY").unwrap_or(String::new());
     let target_env = env::var("CARGO_CFG_TARGET_ENV").unwrap_or(String::new());
@@ -26,6 +36,17 @@ fn main() {
     }
 }
 
+fn rustc_minor_version() -> Option<u32> {
+    let rustc = env::var_os("RUSTC")?;
+    let output = Command::new(rustc).arg("--version").output().ok()?;
+    let version = std::str::from_utf8(&output.stdout).ok()?;
+    let mut pieces = version.split('.');
+    if pieces.next() != Some("rustc 1") {
+        return None;
+    }
+    pieces.next()?.parse().ok()
+}
+
 fn link_lib(name: &str) {
     let out_dir = PathBuf::from(env::var_os("OUT_DIR").unwrap());
     let mut src = env::current_dir().unwrap();
diff --git a/crates/guest-rust/src/rt/mod.rs b/crates/guest-rust/src/rt/mod.rs
index 27e233695..df7141fe9 100644
--- a/crates/guest-rust/src/rt/mod.rs
+++ b/crates/guest-rust/src/rt/mod.rs
@@ -200,20 +200,24 @@ pub unsafe fn cabi_realloc(
 /// `cabi_realloc`, which is a *core* export func, but should not execute ctors.
 #[cfg(target_arch = "wasm32")]
 pub fn run_ctors_once() {
-    static mut RUN: bool = false;
-    unsafe {
-        if !RUN {
-            // This function is synthesized by `wasm-ld` to run all static
-            // constructors. wasm-ld will either provide an implementation
-            // of this symbol, or synthesize a wrapper around each
-            // exported function to (unconditionally) run ctors. By using
-            // this function, the linked module is opting into "manually"
-            // running ctors.
-            unsafe extern "C" {
-                fn __wasm_call_ctors();
+    #[cfg(not(wasi_has_initialize))]
+    {
+        static mut RUN: bool = false;
+
+        unsafe {
+            if !RUN {
+                // This function is synthesized by `wasm-ld` to run all static
+                // constructors. wasm-ld will either provide an implementation
+                // of this symbol, or synthesize a wrapper around each
+                // exported function to (unconditionally) run ctors. By using
+                // this function, the linked module is opting into "manually"
+                // running ctors.
+                unsafe extern "C" {
+                    fn __wasm_call_ctors();
+                }
+                __wasm_call_ctors();
+                RUN = true;
             }
-            __wasm_call_ctors();
-            RUN = true;
         }
     }
 }
diff --git a/tests/runtime/rust/ctors-run-once/runner.rs b/tests/runtime/rust/ctors-run-once/runner.rs
new file mode 100644
index 000000000..3d34844e3
--- /dev/null
+++ b/tests/runtime/rust/ctors-run-once/runner.rs
@@ -0,0 +1,14 @@
+include!(env!("BINDINGS"));
+
+struct Component;
+
+export!(Component);
+
+impl Guest for Component {
+    fn run() {
+        // Startup may have run the constructors at instantiation or at the
+        // first export call. Neither export call should run them again.
+        assert_eq!(the::test::i::ctor_runs(), 1);
+        assert_eq!(the::test::i::ctor_runs(), 1);
+    }
+}
diff --git a/tests/runtime/rust/ctors-run-once/test.rs b/tests/runtime/rust/ctors-run-once/test.rs
new file mode 100644
index 000000000..b73434cda
--- /dev/null
+++ b/tests/runtime/rust/ctors-run-once/test.rs
@@ -0,0 +1,23 @@
+include!(env!("BINDINGS"));
+
+use std::sync::atomic::{AtomicU32, Ordering::Relaxed};
+
+static CTOR_RUNS: AtomicU32 = AtomicU32::new(0);
+
+extern "C" fn ctor() {
+    CTOR_RUNS.fetch_add(1, Relaxed);
+}
+
+#[used]
+#[unsafe(link_section = ".init_array")]
+static CTOR: extern "C" fn() = ctor;
+
+struct Test;
+
+export!(Test);
+
+impl exports::the::test::i::Guest for Test {
+    fn ctor_runs() -> u32 {
+        CTOR_RUNS.load(Relaxed)
+    }
+}
diff --git a/tests/runtime/rust/ctors-run-once/test.wit b/tests/runtime/rust/ctors-run-once/test.wit
new file mode 100644
index 000000000..aa7ff0d72
--- /dev/null
+++ b/tests/runtime/rust/ctors-run-once/test.wit
@@ -0,0 +1,14 @@
+package the:test;
+
+interface i {
+  ctor-runs: func() -> u32;
+}
+
+world runner {
+  import i;
+  export run: func();
+}
+
+world test {
+  export i;
+}