Alan Shearer has the most career goals in the Premier League against Big Six opponents, with 56 goals.

most goals by a player vs the big 6 all-time

	NAME	G	M	MIN	START	G/M	A	G+A	PK	FK	SH	SOT	WOOD	TCH	TCH-BOX	OFF
1	Alan Shearer A. Shearer	56	129	11,314	126	0.43	19	75	7
2	Wayne Rooney W. Rooney	45	135	10,635	117	0.33	14	59	6
3	Jamie Vardy J. Vardy	44	99	7,696	86	0.44	10	54	8	0	177	87	7	2,105	303	83
4	Sergio Agüero S. Agüero	44	75	5,630	69	0.59	8	52	6
5	Mohamed Salah M. Salah	42	71	5,821	66	0.59	17	59	8
6	Jimmy Floyd Hasselbaink J. Floyd Hasselbaink	41	81	5,793	66	0.51	11	52	3
7	Harry Kane H. Kane	39	81	7,007	78	0.48	9	48	11
8	Thierry Henry T. Henry	34	61	5,181	57	0.56	13	47	3
9	Dion Dublin D. Dublin	34	92	7,047	79	0.37	13	47	5
10	Robbie Fowler R. Fowler	33	90	6,386	70	0.37	10	43	3
11	Andrew Cole A. Cole	32	109	8,470	95	0.29	13	45	0
12	Darren Bent D. Bent	31	76	5,287	56	0.41	5	36	4
13	Les Ferdinand L. Ferdinand	31	93	6,907	78	0.33	13	44	0
14	Sadio Mané S. Mané	29	79	6,196	71	0.37	9	38	0	0	153	76	4	3,686	286	65
15	Robin van Persie R. van Persie	28	75	5,554	61	0.37	11	39	3
16	Jermain Defoe J. Defoe	28	136	8,646	91	0.21	6	34	5
17	Mark Viduka M. Viduka	27	74	5,413	59	0.36	3	30	2
18	Marcus Rashford M. Rashford	26	76	5,354	60	0.34	7	33	3	0	121	61	4	2,260	258	36
19	Frank Lampard F. Lampard	26	158	12,798	144	0.16	21	47	10
20	Son Heung-Min S. Heung-Min	25	81	5,907	70	0.31	8	33	1	0	159	73	5	2,909	258	53
21	Roberto Firmino R. Firmino	25	70	5,255	62	0.36	9	34	1	0	149	69	4	3,313	329	24
22	Teddy Sheringham T. Sheringham	25	106	7,846	88	0.24	12	37	5
23	Christian Benteke C. Benteke	24	83	5,792	64	0.29	9	33	1
24	Kevin De Bruyne K. De Bruyne	23	70	5,611	64	0.33	19	42	2
25	Gylfi Sigurdsson G. Sigurdsson	23	98	7,452	82	0.23	11	34	5