The New York Yankees have the highest run differential by a team with 50+ games played, with a differential of 13,119 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	13,119	19,054	.569	10,801	8,165	649,413	92,602	172,416	28,624	5,493	17,311	86,044	68,561	4,927	94,779	11,646	2,800	735,777	263,959	51,428	9,595	3,281	2,830	10,677	.265	.339	.406	.745
2	Giants	7,469	21,764	.535	11,565	10,036	742,790	100,642	195,380	31,340	7,035	15,580	90,116	68,273	5,674	99,524	16,515	3,143	831,415	287,530	53,955	11,664	3,014	4,016	10,178	.263	.329	.387	.716
3	Dodgers	6,240	21,680	.532	11,459	10,082	738,713	97,872	193,009	31,046	7,006	14,119	88,094	68,872	5,146	100,304	17,339	3,550	828,638	280,424	52,171	12,773	3,058	3,732	9,936	.261	.327	.380	.707
4	Red Sox	3,606	19,343	.518	9,977	9,283	662,020	90,337	176,656	33,109	5,598	14,593	83,773	66,788	4,801	95,503	9,630	2,548	747,542	264,740	53,300	10,595	3,338	2,997	11,544	.267	.337	.400	.737
5	Cubs	3,571	22,296	.513	11,350	10,785	763,003	102,653	199,820	33,737	7,356	15,243	88,242	68,549	5,282	105,007	15,781	3,069	852,763	293,998	56,336	13,026	2,903	3,518	9,960	.262	.326	.385	.711
6	Guardians	2,246	19,352	.513	9,875	9,386	659,592	87,497	174,622	31,137	5,496	13,912	80,862	62,603	4,832	94,543	11,905	3,386	741,843	258,487	50,545	11,462	3,354	2,544	10,522	.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	1,951	20,647	.513	10,527	9,989	706,250	92,378	187,684	31,820	7,049	12,853	84,441	64,178	5,196	98,102	15,011	3,614	790,734	272,161	51,722	11,972	3,138	3,775	10,132	.266	.330	.385	.715
9	Braves	1,523	22,257	.504	11,133	10,970	762,037	99,474	197,907	32,100	6,300	15,047	86,522	67,476	5,064	100,087	14,092	3,064	850,137	287,748	53,447	12,683	2,877	3,655	10,376	.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	Reds	760	21,881	.504	10,954	10,788	745,554	98,188	194,245	32,368	7,557	14,314	87,334	66,698	5,505	102,228	18,161	3,404	833,622	284,669	54,239	12,662	3,035	3,646	9,711	.261	.325	.382	.707
13	Astros	727	10,018	.502	5,029	4,984	339,983	42,729	86,669	15,895	2,172	8,414	40,213	32,334	2,896	62,865	7,147	3,130	381,955	132,150	26,481	4,030	2,712	3,144	7,400	.255	.323	.389	.711
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	364	7,592	.498	3,781	3,808	260,125	35,095	67,652	13,519	1,491	8,246	33,288	24,119	2,423	48,921	4,570	1,963	290,291	108,891	23,256	1,499	2,125	1,400	5,919	.260	.326	.419	.745
16	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
17	Tigers	328	19,377	.503	9,702	9,582	660,781	88,984	174,581	29,574	6,295	14,570	81,942	65,530	4,442	96,665	11,289	2,936	744,868	260,455	50,439	11,009	3,106	2,446	10,713	.264	.333	.394	.727
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