The New York Yankees have the highest run differential by a team with 2+ games played, with a differential of 13,143 runs.

Interpreted as:

largest run differential in two or more game

	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	13,143	19,102	.569	10,826	8,188	651,043	92,817	172,818	28,703	5,501	17,376	86,247	68,754	4,940	95,207	11,679	2,810	737,630	264,651	51,580	9,598	3,295	2,850	10,714	.265	.339	.407	.745
2	Giants	7,464	21,811	.535	11,588	10,060	744,317	100,817	195,733	31,408	7,045	15,619	90,281	68,446	5,696	99,912	16,536	3,151	833,165	288,088	54,072	11,676	3,030	4,020	10,216	.263	.329	.387	.716
3	Dodgers	6,282	21,727	.532	11,488	10,100	740,325	98,138	193,426	31,125	7,012	14,193	88,351	69,048	5,164	100,673	17,356	3,555	830,461	281,154	52,330	12,774	3,074	3,744	9,969	.261	.327	.380	.707
4	Cubs	3,638	22,343	.513	11,380	10,802	764,616	102,895	200,239	33,818	7,365	15,317	88,479	68,693	5,294	105,357	15,834	3,078	854,550	294,738	56,500	13,028	2,919	3,525	9,978	.262	.326	.385	.711
5	Red Sox	3,601	19,390	.518	9,999	9,308	663,634	90,564	177,062	33,205	5,605	14,651	83,991	66,941	4,825	95,945	9,661	2,558	749,349	265,430	53,461	10,599	3,350	3,003	11,573	.267	.337	.400	.737
6	Guardians	2,211	19,397	.512	9,892	9,414	661,057	87,642	174,940	31,198	5,502	13,951	81,003	62,738	4,846	94,928	11,940	3,397	743,472	258,995	50,651	11,467	3,364	2,551	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	1,951	20,695	.513	10,552	10,012	707,871	92,590	188,077	31,890	7,052	12,903	84,644	64,309	5,225	98,477	15,030	3,620	792,534	272,780	51,845	11,977	3,152	3,779	10,159	.266	.330	.385	.715
9	Braves	1,534	22,303	.504	11,153	10,996	763,592	99,665	198,295	32,159	6,304	15,093	86,707	67,641	5,077	100,488	14,110	3,071	851,886	288,341	53,556	12,686	2,890	3,661	10,406	.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	774	21,927	.504	10,980	10,808	747,098	98,403	194,642	32,448	7,565	14,366	87,535	66,834	5,517	102,615	18,180	3,414	835,334	285,318	54,379	12,666	3,051	3,649	9,748	.261	.325	.382	.707
13	Astros	754	10,066	.503	5,061	5,000	341,604	42,933	87,099	15,961	2,176	8,474	40,408	32,455	2,920	63,221	7,172	3,142	383,734	132,834	26,611	4,031	2,724	3,146	7,443	.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	395	7,639	.499	3,810	3,826	261,717	35,340	68,075	13,596	1,494	8,308	33,522	24,284	2,441	49,210	4,590	1,969	292,087	109,583	23,398	1,509	2,136	1,409	5,957	.260	.326	.419	.745
16	Tigers	365	19,424	.503	9,730	9,601	662,378	89,216	174,992	29,659	6,307	14,631	82,163	65,667	4,465	97,061	11,302	2,940	746,644	261,158	50,597	11,010	3,124	2,450	10,733	.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