The New York Yankees have the highest run differential by a team with 20+ games played, with a differential of 13,151 runs.

Interpreted as:

largest run diffrential in 20 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	13,151	19,066	.570	10,810	8,168	649,820	92,663	172,522	28,648	5,497	17,327	86,101	68,611	4,929	94,880	11,654	2,801	736,243	264,145	51,472	9,595	3,288	2,835	10,687	.265	.339	.406	.745
2	Giants	7,478	21,776	.535	11,572	10,041	743,183	100,688	195,472	31,355	7,038	15,592	90,160	68,321	5,677	99,622	16,517	3,146	831,862	287,679	53,985	11,666	3,015	4,018	10,186	.263	.329	.387	.716
3	Dodgers	6,243	21,691	.532	11,464	10,088	739,093	97,937	193,108	31,064	7,006	14,136	88,157	68,919	5,153	100,386	17,344	3,551	829,077	280,592	52,206	12,774	3,062	3,736	9,948	.261	.327	.380	.707
4	Cubs	3,612	22,308	.513	11,359	10,788	763,435	102,741	199,951	33,768	7,360	15,262	88,326	68,590	5,285	105,093	15,796	3,071	853,246	294,225	56,390	13,026	2,910	3,521	9,964	.262	.326	.385	.711
5	Red Sox	3,595	19,356	.518	9,982	9,291	662,471	90,399	176,772	33,133	5,600	14,612	83,834	66,827	4,807	95,617	9,637	2,552	748,041	264,941	53,345	10,596	3,340	2,997	11,550	.267	.337	.400	.737
6	Guardians	2,252	19,364	.513	9,881	9,392	659,986	87,542	174,710	31,155	5,499	13,922	80,906	62,638	4,838	94,641	11,913	3,389	742,283	258,629	50,576	11,463	3,358	2,545	10,528	.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	1,970	20,659	.513	10,535	9,993	706,653	92,438	187,790	31,838	7,050	12,863	84,498	64,202	5,204	98,189	15,017	3,616	791,177	272,317	51,751	11,974	3,144	3,776	10,139	.266	.330	.385	.715
9	Braves	1,536	22,269	.504	11,139	10,976	762,449	99,533	198,024	32,116	6,301	15,061	86,579	67,514	5,069	100,185	14,100	3,067	850,597	287,925	53,478	12,684	2,881	3,655	10,387	.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	761	21,893	.504	10,960	10,794	745,958	98,238	194,354	32,399	7,560	14,326	87,380	66,727	5,508	102,332	18,168	3,409	834,061	284,851	54,285	12,662	3,038	3,646	9,720	.261	.325	.382	.707
13	Astros	730	10,032	.502	5,037	4,990	340,447	42,780	86,794	15,912	2,173	8,430	40,261	32,366	2,906	62,961	7,149	3,136	382,465	132,342	26,515	4,030	2,716	3,145	7,416	.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	359	7,604	.498	3,786	3,815	260,516	35,144	67,742	13,535	1,492	8,261	33,334	24,163	2,426	49,005	4,576	1,963	290,733	109,044	23,288	1,502	2,126	1,402	5,933	.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	335	19,390	.503	9,710	9,587	661,227	89,048	174,691	29,602	6,295	14,584	82,000	65,569	4,450	96,774	11,292	2,938	745,365	260,635	50,481	11,009	3,110	2,447	10,718	.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