The Minnesota Twins had the highest run differential by a team in 1965, with a differential of 174 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	Twins	174	1965	162	.630	102	60	5,488	774	1,396	257	42	150	711	554	35	969	92	33	6,213	2,187	449	77	59	79	93	.254	.324	.399	.722
2	Reds	121	1965	162	.549	89	73	5,658	825	1,544	268	61	183	776	538	50	1,003	82	40	6,355	2,483	512	73	36	89	120	.273	.339	.439	.778
3	Pirates	95	1965	163	.556	90	72	5,686	675	1,506	217	57	111	631	419	35	1,008	51	38	6,249	2,170	385	67	42	75	138	.265	.317	.382	.699
4	White Sox	92	1965	162	.586	95	67	5,509	647	1,354	200	38	125	587	533	43	916	50	33	6,217	2,005	363	89	43	62	127	.246	.315	.364	.679
5	Giants	89	1965	163	.586	95	67	5,495	682	1,384	169	43	159	623	476	31	844	47	27	6,119	2,116	371	80	37	68	149	.252	.313	.385	.698
6	Dodgers	87	1965	162	.599	97	65	5,425	608	1,329	193	32	78	548	492	52	891	172	77	6,107	1,820	303	103	35	57	79	.245	.312	.335	.647
7	Tigers	78	1965	162	.549	89	73	5,368	680	1,278	190	27	162	634	554	37	952	57	41	6,064	2,008	379	69	36	50	122	.238	.312	.374	.686
8	Braves	75	1965	162	.531	86	76	5,542	708	1,419	243	28	196	664	408	37	976	64	37	6,077	2,306	467	58	32	50	121	.256	.310	.416	.726
9	Orioles	63	1965	162	.580	94	68	5,450	641	1,299	227	38	125	596	529	28	907	67	31	6,138	1,977	390	95	36	61	139	.238	.307	.363	.670
10	Indians	50	1965	162	.537	87	75	5,469	663	1,367	198	21	156	615	506	33	857	109	46	6,138	2,075	375	90	40	63	97	.250	.315	.379	.695
11	Cardinals	33	1965	162	.497	80	81	5,579	707	1,415	234	46	109	645	477	35	882	100	52	6,204	2,068	389	72	41	49	98	.254	.314	.371	.685
12	Yankees	7	1965	162	.475	77	85	5,470	611	1,286	196	31	149	576	489	19	951	35	20	6,081	1,991	376	72	31	62	118	.235	.299	.364	.663
13	Phillies	-13	1965	162	.528	85	76	5,528	654	1,380	205	53	144	608	494	36	1,091	46	32	6,172	2,123	402	75	39	60	115	.250	.313	.384	.697
14	Angels	-42	1965	162	.463	75	87	5,354	527	1,279	200	36	92	486	443	22	973	107	57	5,956	1,827	328	93	44	48	99	.239	.297	.341	.639
15	Cubs	-88	1965	164	.444	72	90	5,540	635	1,316	202	33	134	590	532	43	948	65	47	6,205	1,986	369	48	42	62	115	.238	.307	.358	.666
16	Red Sox	-122	1965	162	.383	62	100	5,487	669	1,378	244	40	165	629	607	30	964	47	24	6,220	2,197	449	57	39	44	157	.251	.327	.400	.727
17	Senators	-130	1965	162	.432	70	92	5,374	591	1,227	179	33	136	563	570	34	1,125	30	19	6,078	1,880	348	63	37	36	112	.228	.304	.350	.654
18	Astros	-142	1965	162	.401	65	97	5,483	569	1,299	188	42	97	523	502	46	877	90	37	6,122	1,862	327	57	34	46	125	.237	.305	.340	.644
19	Athletics	-170	1965	162	.364	59	103	5,393	585	1,294	186	59	110	546	521	35	1,020	110	51	6,058	1,928	355	74	35	29	120	.240	.309	.358	.667
20	Mets	-257	1965	164	.309	50	112	5,441	495	1,202	203	27	107	460	392	39	1,129	28	42	5,976	1,780	337	76	28	40	121	.221	.277	.327	.604