Between the 2000 and 2022 seasons, the Kansas City Royals had the lowest run differential by a team, with a differential of -2,225 runs.

	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	Royals	-2,225	3,624	.440	1,595	2,029	124,281	15,827	32,601	6,317	784	3,123	14,970	9,763	1,228	23,981	2,444	888	137,134	49,855	10,224	840	1,022	561	2,893	.262	.320	.401	.721
2	Pirates	-2,065	3,620	.446	1,615	2,004	122,755	15,117	30,939	6,186	706	3,307	14,405	10,875	1,503	27,070	1,810	868	137,264	48,458	10,199	1,241	890	838	2,648	.252	.318	.395	.713
3	Orioles	-2,039	3,624	.445	1,613	2,009	124,434	16,150	32,112	6,284	446	4,140	15,423	10,380	1,258	25,628	1,830	736	137,648	51,708	10,870	638	938	563	2,853	.258	.319	.416	.735
4	Tigers	-1,327	3,619	.463	1,677	1,942	124,282	16,242	32,659	6,271	862	3,724	15,534	10,591	1,105	26,562	1,634	771	137,694	51,826	10,857	717	999	647	2,866	.263	.324	.417	.741
5	Marlins	-1,286	3,620	.465	1,685	1,935	122,978	15,281	31,295	6,110	708	3,388	14,494	10,968	1,356	28,016	2,267	872	137,462	48,985	10,206	1,267	893	893	2,679	.254	.320	.398	.719
6	Reds	-1,155	3,626	.470	1,702	1,922	123,060	16,112	31,087	6,153	530	4,155	15,388	11,931	1,501	28,178	2,089	849	138,732	50,765	10,838	1,351	889	912	2,619	.253	.324	.413	.737
7	Padres	-1,103	3,625	.473	1,713	1,912	122,361	15,140	30,199	5,868	685	3,400	14,392	11,970	1,114	28,150	2,187	812	137,521	47,637	9,953	1,125	951	817	2,591	.247	.317	.389	.707
8	Rockies	-854	3,625	.466	1,689	1,936	124,461	17,776	33,476	6,683	946	4,011	16,917	11,634	1,105	27,464	2,035	878	139,628	54,084	11,640	1,460	968	921	2,713	.269	.334	.435	.769
9	Nationals	-606	3,622	.479	1,736	1,886	122,468	15,799	31,317	6,376	609	3,654	15,031	11,779	1,266	26,674	2,072	841	137,854	49,873	10,639	1,409	932	1,011	2,797	.256	.325	.407	.732
10	Brewers	-507	3,625	.490	1,775	1,849	122,583	16,075	30,844	6,257	618	4,217	15,367	11,820	1,533	29,132	2,279	821	138,005	50,988	11,092	1,197	872	882	2,745	.252	.323	.416	.739
11	Rangers	-459	3,625	.488	1,769	1,856	124,621	17,703	32,690	6,480	622	4,482	16,853	11,211	1,330	26,709	2,212	817	138,893	53,860	11,584	709	1,022	642	2,651	.262	.327	.432	.760
12	Diamondbacks	-453	3,624	.483	1,749	1,875	123,664	16,300	31,414	6,548	884	3,793	15,543	11,993	1,147	27,459	1,970	758	138,927	51,109	11,225	1,141	982	972	2,597	.254	.323	.413	.737
13	Mariners	-343	3,624	.497	1,802	1,822	123,758	15,897	31,523	5,936	550	3,708	15,123	11,305	1,230	26,351	2,240	852	137,997	49,683	10,194	746	958	733	2,643	.255	.321	.401	.722
14	Rays	-338	3,622	.491	1,780	1,842	123,160	16,130	31,206	6,288	728	3,819	15,363	11,795	1,389	27,959	2,618	997	137,967	50,407	10,835	638	985	615	2,512	.253	.323	.409	.733
15	Twins	-167	3,625	.501	1,815	1,810	124,464	16,755	32,576	6,570	714	3,658	15,889	11,563	1,163	25,714	1,910	812	138,876	51,548	10,942	668	1,018	721	2,853	.262	.328	.414	.742
16	White Sox	-96	3,624	.499	1,809	1,815	123,549	16,703	32,110	6,048	536	4,288	16,004	10,674	1,412	26,069	2,012	919	137,414	52,094	10,872	833	946	519	2,834	.260	.324	.422	.745
17	Mets	53	3,622	.500	1,812	1,810	122,897	15,817	31,138	6,179	609	3,727	15,080	11,856	1,377	26,272	2,123	767	138,296	49,716	10,515	1,254	912	1,017	2,720	.253	.324	.405	.728
18	Phillies	106	3,623	.506	1,834	1,789	123,788	16,540	31,479	6,331	734	3,981	15,761	12,312	1,349	27,366	2,241	624	139,511	51,221	11,046	1,168	894	1,081	2,520	.254	.326	.414	.740
19	Cubs	180	3,623	.498	1,803	1,819	123,216	16,182	31,316	6,347	646	4,062	15,401	11,789	1,408	28,075	1,678	761	138,565	51,141	11,055	1,287	865	914	2,746	.254	.324	.415	.739
20	Blue Jays	427	3,623	.501	1,814	1,809	124,163	17,253	32,155	6,753	528	4,488	16,487	11,611	1,269	25,879	1,734	660	138,553	53,428	11,769	529	981	549	2,905	.259	.326	.430	.757
21	Giants	563	3,622	.523	1,893	1,728	123,419	15,916	31,748	6,388	798	3,484	15,140	11,650	1,142	25,273	1,642	710	138,517	50,184	10,670	1,277	1,029	1,200	2,858	.257	.325	.407	.731
22	Angels	635	3,624	.524	1,898	1,726	123,902	16,814	32,485	6,226	608	3,852	16,008	11,011	1,246	24,390	2,451	967	137,974	51,483	10,686	793	1,022	838	2,813	.262	.326	.416	.742
23	Astros	670	3,624	.511	1,851	1,772	123,163	16,641	31,767	6,405	582	4,136	15,873	11,748	1,359	26,251	2,062	846	138,354	51,744	11,123	1,110	974	768	2,885	.258	.327	.420	.747
24	Guardians	847	3,622	.518	1,878	1,744	123,761	17,137	32,184	6,710	580	3,977	16,342	12,254	1,406	26,242	2,084	777	139,263	51,985	11,267	786	1,056	690	2,778	.260	.331	.420	.751
25	Athletics	1,161	3,622	.528	1,911	1,711	123,469	16,727	31,031	6,449	533	3,959	15,925	12,686	1,282	25,893	1,627	554	138,914	50,423	10,941	479	998	583	2,876	.251	.325	.408	.733