The New York Yankees had the highest run differential by a team in 1961, with a differential of 215 runs.

	TEAM	DIFF	SEASON	G	W%	W	L	AB	R	H	2B	3B	HR	RBI	BB	HBP	SO	SB	CS	PA	TB	XBH	SH	SF	IBB	GIDP	AVG	OBP	SLG	OPS
1	Yankees	215	1961	163	.673	109	53	5,559	827	1,461	194	40	240	781	543	35	785	28	18	6,239	2,455	474	57	45	45	120	.263	.330	.442	.771
2	Tigers	170	1961	163	.623	101	61	5,561	841	1,481	215	53	180	779	673	38	865	98	36	6,378	2,342	448	64	42	39	125	.266	.347	.421	.768
3	Giants	118	1961	155	.552	85	69	5,233	773	1,379	219	32	183	709	506	30	764	79	54	5,887	2,211	434	70	48	58	124	.264	.329	.423	.752
4	Orioles	103	1961	163	.586	95	67	5,481	691	1,393	227	36	149	638	581	23	902	39	30	6,211	2,139	412	78	48	25	140	.254	.326	.390	.716
5	Reds	57	1961	154	.604	93	61	5,243	710	1,414	247	35	158	675	423	29	761	70	33	5,796	2,205	440	50	51	59	109	.270	.325	.421	.745
6	Braves	56	1961	155	.539	83	71	5,288	712	1,365	199	34	188	662	534	34	880	70	43	5,958	2,196	421	62	40	50	133	.258	.328	.415	.743
7	White Sox	39	1961	163	.531	86	76	5,556	765	1,475	216	46	138	704	550	57	612	100	40	6,285	2,197	400	71	51	30	118	.265	.335	.395	.730
8	Dodgers	38	1961	154	.578	89	65	5,189	735	1,358	193	40	157	673	596	23	796	86	45	5,940	2,102	390	96	36	53	117	.262	.338	.405	.743
9	Cardinals	35	1961	155	.519	80	74	5,307	703	1,436	236	51	103	657	494	33	745	46	28	5,944	2,083	390	70	40	61	108	.271	.334	.393	.727
10	Pirates	19	1961	154	.487	75	79	5,311	694	1,448	232	57	128	646	428	27	721	26	30	5,867	2,178	417	64	37	51	140	.273	.328	.410	.738
11	Indians	-15	1961	161	.484	78	83	5,609	737	1,493	257	39	150	682	492	28	720	34	11	6,252	2,278	446	73	50	33	133	.266	.326	.406	.732
12	Angels	-40	1961	162	.435	70	91	5,424	744	1,331	218	22	189	700	681	30	1,068	37	28	6,252	2,160	429	80	37	25	116	.245	.331	.398	.729
13	Red Sox	-63	1961	163	.469	76	86	5,508	729	1,401	251	37	112	682	647	29	846	56	36	6,307	2,062	400	81	42	28	129	.254	.334	.374	.708
14	Twins	-71	1961	161	.438	70	90	5,417	707	1,353	215	40	167	665	597	33	840	47	43	6,156	2,149	422	67	42	25	141	.250	.326	.397	.722
15	Cubs	-111	1961	156	.416	64	90	5,344	689	1,364	238	51	176	650	539	32	1,027	35	25	6,000	2,232	465	52	33	64	115	.255	.325	.418	.743
16	Senators	-158	1961	161	.379	61	100	5,366	618	1,307	217	44	119	578	558	21	917	81	47	6,062	1,969	380	73	44	30	127	.244	.315	.367	.682
17	Athletics	-180	1961	162	.379	61	100	5,423	683	1,342	216	47	90	631	580	25	770	58	22	6,164	1,922	353	89	47	10	107	.247	.320	.354	.675
18	Phillies	-212	1961	155	.305	47	107	5,213	584	1,265	185	50	103	549	475	46	928	56	30	5,870	1,859	338	108	28	46	130	.243	.310	.357	.667