diff --git a/notifier/notifier.go b/notifier/notifier.go
index b7f719ea58..482d2fdaab 100644
--- a/notifier/notifier.go
+++ b/notifier/notifier.go
@@ -16,6 +16,8 @@ package notifier
 import (
 	"bytes"
 	"context"
+	"crypto/md5"
+	"encoding/hex"
 	"encoding/json"
 	"fmt"
 	"io"
@@ -35,6 +37,7 @@ import (
 	"github.com/prometheus/common/sigv4"
 	"github.com/prometheus/common/version"
 	"go.uber.org/atomic"
+	"gopkg.in/yaml.v2"
 
 	"github.com/prometheus/prometheus/config"
 	"github.com/prometheus/prometheus/discovery/targetgroup"
@@ -257,6 +260,16 @@ func (n *Manager) ApplyConfig(conf *config.Config) error {
 	n.opts.RelabelConfigs = conf.AlertingConfig.AlertRelabelConfigs
 
 	amSets := make(map[string]*alertmanagerSet)
+	// configToAlertmanagers maps alertmanager sets for each unique AlertmanagerConfig,
+	// helping to avoid dropping known alertmanagers and re-use them without waiting for SD updates when applying the config.
+	configToAlertmanagers := make(map[string]*alertmanagerSet, len(n.alertmanagers))
+	for _, oldAmSet := range n.alertmanagers {
+		hash, err := oldAmSet.configHash()
+		if err != nil {
+			return err
+		}
+		configToAlertmanagers[hash] = oldAmSet
+	}
 
 	for k, cfg := range conf.AlertingConfig.AlertmanagerConfigs.ToMap() {
 		ams, err := newAlertmanagerSet(cfg, n.logger, n.metrics)
@@ -264,6 +277,16 @@ func (n *Manager) ApplyConfig(conf *config.Config) error {
 			return err
 		}
 
+		hash, err := ams.configHash()
+		if err != nil {
+			return err
+		}
+
+		if oldAmSet, ok := configToAlertmanagers[hash]; ok {
+			ams.ams = oldAmSet.ams
+			ams.droppedAms = oldAmSet.droppedAms
+		}
+
 		amSets[k] = ams
 	}
 
@@ -803,6 +826,15 @@ func (s *alertmanagerSet) sync(tgs []*targetgroup.Group) {
 	}
 }
 
+func (s *alertmanagerSet) configHash() (string, error) {
+	b, err := yaml.Marshal(s.cfg)
+	if err != nil {
+		return "", err
+	}
+	hash := md5.Sum(b)
+	return hex.EncodeToString(hash[:]), nil
+}
+
 func postPath(pre string, v config.AlertmanagerAPIVersion) string {
 	alertPushEndpoint := fmt.Sprintf("/api/%v/alerts", string(v))
 	return path.Join("/", pre, alertPushEndpoint)
diff --git a/notifier/notifier_test.go b/notifier/notifier_test.go
index ac722eb23c..83eaf8168b 100644
--- a/notifier/notifier_test.go
+++ b/notifier/notifier_test.go
@@ -38,6 +38,7 @@ import (
 	"github.com/prometheus/prometheus/discovery"
 
 	"github.com/prometheus/prometheus/config"
+	_ "github.com/prometheus/prometheus/discovery/file"
 	"github.com/prometheus/prometheus/discovery/targetgroup"
 	"github.com/prometheus/prometheus/model/labels"
 	"github.com/prometheus/prometheus/model/relabel"
@@ -1017,3 +1018,107 @@ func TestStop_DrainingEnabled(t *testing.T) {
 
 	require.Equal(t, int64(2), alertsReceived.Load())
 }
+
+func TestApplyConfig(t *testing.T) {
+	targetURL := "alertmanager:9093"
+	targetGroup := &targetgroup.Group{
+		Targets: []model.LabelSet{
+			{
+				"__address__": model.LabelValue(targetURL),
+			},
+		},
+	}
+	alertmanagerURL := fmt.Sprintf("http://%s/api/v2/alerts", targetURL)
+
+	n := NewManager(&Options{}, nil)
+	cfg := &config.Config{}
+	s := `
+alerting:
+  alertmanagers:
+  - file_sd_configs:
+    - files:
+      - foo.json
+`
+	// 1. Ensure known alertmanagers are not dropped during ApplyConfig.
+	require.NoError(t, yaml.UnmarshalStrict([]byte(s), cfg))
+	require.Len(t, cfg.AlertingConfig.AlertmanagerConfigs, 1)
+
+	// First, apply the config and reload.
+	require.NoError(t, n.ApplyConfig(cfg))
+	tgs := map[string][]*targetgroup.Group{"config-0": {targetGroup}}
+	n.reload(tgs)
+	require.Len(t, n.Alertmanagers(), 1)
+	require.Equal(t, alertmanagerURL, n.Alertmanagers()[0].String())
+
+	// Reapply the config.
+	require.NoError(t, n.ApplyConfig(cfg))
+	// Ensure the known alertmanagers are not dropped.
+	require.Len(t, n.Alertmanagers(), 1)
+	require.Equal(t, alertmanagerURL, n.Alertmanagers()[0].String())
+
+	// 2. Ensure known alertmanagers are not dropped during ApplyConfig even when
+	// the config order changes.
+	s = `
+alerting:
+  alertmanagers:
+  - static_configs:
+  - file_sd_configs:
+    - files:
+      - foo.json
+`
+	require.NoError(t, yaml.UnmarshalStrict([]byte(s), cfg))
+	require.Len(t, cfg.AlertingConfig.AlertmanagerConfigs, 2)
+
+	require.NoError(t, n.ApplyConfig(cfg))
+	require.Len(t, n.Alertmanagers(), 1)
+	// Ensure no unnecessary alertmanagers are injected.
+	require.Empty(t, n.alertmanagers["config-0"].ams)
+	// Ensure the config order is taken into account.
+	ams := n.alertmanagers["config-1"].ams
+	require.Len(t, ams, 1)
+	require.Equal(t, alertmanagerURL, ams[0].url().String())
+
+	// 3. Ensure known alertmanagers are reused for new config with identical AlertmanagerConfig.
+	s = `
+alerting:
+  alertmanagers:
+  - file_sd_configs:
+    - files:
+      - foo.json
+  - file_sd_configs:
+    - files:
+      - foo.json
+`
+	require.NoError(t, yaml.UnmarshalStrict([]byte(s), cfg))
+	require.Len(t, cfg.AlertingConfig.AlertmanagerConfigs, 2)
+
+	require.NoError(t, n.ApplyConfig(cfg))
+	require.Len(t, n.Alertmanagers(), 2)
+	for cfgIdx := range 2 {
+		ams := n.alertmanagers[fmt.Sprintf("config-%d", cfgIdx)].ams
+		require.Len(t, ams, 1)
+		require.Equal(t, alertmanagerURL, ams[0].url().String())
+	}
+
+	// 4. Ensure known alertmanagers are reused only for identical AlertmanagerConfig.
+	s = `
+alerting:
+  alertmanagers:
+  - file_sd_configs:
+    - files:
+      - foo.json
+    path_prefix: /bar
+  - file_sd_configs:
+    - files:
+      - foo.json
+    relabel_configs:
+    - source_labels: ['__address__']
+      regex: 'doesntmatter:1234'
+      action: drop
+`
+	require.NoError(t, yaml.UnmarshalStrict([]byte(s), cfg))
+	require.Len(t, cfg.AlertingConfig.AlertmanagerConfigs, 2)
+
+	require.NoError(t, n.ApplyConfig(cfg))
+	require.Empty(t, n.Alertmanagers())
+}