The New York Yankees have the highest run differential by a team with 50+ games played, with a differential of 13,137 runs.

Interpreted as:

highest run differential in 50 or more games

	TEAM	DIFF	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	13,137	19,103	.569	10,826	8,189	651,079	92,823	172,827	28,705	5,501	17,379	86,253	68,756	4,940	95,214	11,679	2,810	737,668	264,671	51,585	9,598	3,295	2,850	10,714	.265	.339	.407	.745
2	Giants	7,460	21,813	.535	11,589	10,061	744,387	100,826	195,749	31,414	7,045	15,621	90,289	68,452	5,699	99,929	16,536	3,151	833,244	288,116	54,080	11,676	3,030	4,021	10,216	.263	.329	.387	.716
3	Dodgers	6,263	21,729	.532	11,488	10,102	740,394	98,143	193,441	31,126	7,012	14,196	88,356	69,057	5,165	100,690	17,358	3,555	830,540	281,179	52,334	12,774	3,074	3,744	9,970	.261	.327	.380	.707
4	Cubs	3,636	22,344	.513	11,380	10,803	764,652	102,901	200,248	33,821	7,365	15,319	88,484	68,699	5,294	105,366	15,836	3,078	854,592	294,756	56,505	13,028	2,919	3,525	9,978	.262	.326	.385	.711
5	Red Sox	3,608	19,391	.518	10,000	9,308	663,674	90,574	177,073	33,210	5,606	14,652	84,000	66,942	4,825	95,951	9,661	2,558	749,390	265,451	53,468	10,599	3,350	3,003	11,573	.267	.337	.400	.737
6	Guardians	2,209	19,399	.512	9,892	9,416	661,122	87,643	174,953	31,202	5,502	13,952	81,004	62,744	4,846	94,942	11,941	3,398	743,543	259,015	50,656	11,467	3,364	2,552	10,551	.265	.331	.392	.723
7	Browns	2,020	1,233	.644	781	432	43,777	7,933	11,555	1,658	602	304	4,657	3,473	353	436	2,307		47,743	15,329	2,564					.264	.325	.350	.675
8	Cardinals	1,953	20,696	.513	10,553	10,012	707,909	92,598	188,090	31,890	7,052	12,906	84,652	64,311	5,225	98,485	15,030	3,620	792,574	272,802	51,848	11,977	3,152	3,779	10,161	.266	.330	.385	.715
9	Braves	1,529	22,306	.503	11,153	10,999	763,695	99,674	198,318	32,165	6,304	15,097	86,716	67,648	5,080	100,517	14,110	3,071	851,999	288,382	53,566	12,686	2,890	3,661	10,409	.260	.323	.378	.701
10	Orioles	1,512	1,294	.579	730	530	45,361	8,530	13,521	1,814	865	218	6,940	4,345	992	2,952	2,993		51,317	17,719	2,897	619				.298	.372	.391	.763
11	Grays	909	725	.612	438	278	26,572	4,037	6,764	1,084	341	98	292	1,192					27,764	8,824	1,523					.255		.332
12	Astros	773	10,068	.503	5,063	5,000	341,682	42,957	87,128	15,969	2,177	8,480	40,430	32,464	2,921	63,239	7,172	3,143	383,824	132,891	26,626	4,031	2,726	3,147	7,445	.255	.323	.389	.712
13	Reds	770	21,928	.504	10,980	10,809	747,133	98,404	194,650	32,450	7,565	14,367	87,536	66,836	5,517	102,622	18,180	3,414	835,371	285,331	54,382	12,666	3,051	3,649	9,749	.261	.325	.382	.707
14	Reds	578	269	.659	174	90	9,515	2,020	2,647	386	176	106	1,548	1,303	109	499	859		10,927	3,703	668					.278	.371	.389	.761
15	Blue Jays	397	7,641	.499	3,812	3,826	261,793	35,348	68,093	13,597	1,494	8,309	33,529	24,290	2,441	49,225	4,590	1,969	292,171	109,605	23,400	1,511	2,136	1,412	5,959	.260	.326	.419	.745
16	Tigers	367	19,426	.503	9,732	9,601	662,438	89,219	175,001	29,659	6,307	14,634	82,166	65,674	4,466	97,078	11,302	2,941	746,712	261,176	50,600	11,010	3,124	2,450	10,735	.264	.333	.394	.727
17	Athletics	356	1,219	.529	633	564	43,556	7,481	11,208	1,782	741	284	4,168	3,158	351	548	1,900		47,191	15,324	2,807					.257	.315	.352	.666
18	Outlaw Reds	237	105	.657	69	36	3,786	703	1,027	118	63	26		147		482			3,933	1,349	207					.271		.356
19	Whales	207	312	.565	173	133	10,231	1,262	2,634	412	127	102	1,102	964	71	1,200	332		11,614	3,606	641	348				.257	.326	.352	.678
20	Dark Blues	198	129	.619	78	48	5,022	770	1,348	159	53	6		69					5,091	1,631	218					.268		.325
21	Peppers	163	312	.551	168	137	10,273	1,347	2,757	440	170	50	1,116	908	72	1,160	457		11,678	3,687	660	425				.268	.332	.359	.691
22	Giants	143	132	.565	74	57	4,913	1,018	1,393	204	97	66	793	486	31	364	231		5,430	1,989	367					.284	.352	.405	.757
23	Brown Stockings	123	124	.589	73	51	4,656	670	1,173	124	63	3		116					4,772	1,432	190					.252		.308
24	Pirates	116	138	.547	75	62	4,968	886	1,311	200	95	31	705	492	43	410	276		5,503	1,794	326					.264	.335	.361	.697
25	Maroons	90	351	.504	173	170	12,293	1,824	3,081	563	108	70	684	630			156		12,923	4,070	741					.251		.331