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

most goals by a player against big six premier league all-time

	NAME	G	Rating	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	Mohamed Salah M. Salah	50		84	6,976	79	0.60	22	72	11
3	Jamie Vardy J. Vardy	45		108	8,408	95	0.42	10	55	8	0	188	92	8	2,258	328	88
4	Wayne Rooney W. Rooney	45		135	10,635	117	0.33	14	59	6
5	Sergio Agüero S. Agüero	44		75	5,630	69	0.59	8	52	6
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	Andy 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	Marcus Rashford M. Rashford	27		82	5,719	64	0.33	9	36	4	0	130	65	6	2,436	274	39
18	Son Heung-min S. Heung-min	27		88	6,420	76	0.31	9	36	1	0	173	79	5	3,170	289	59
19	Mark Viduka M. Viduka	27		74	5,413	59	0.36	3	30	2
20	Frank Lampard F. Lampard	26		158	12,798	144	0.16	21	47	10
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	Erling Haaland E. Haaland	23	7.30	31	2,697	30	0.74	8	31	3	0	104	54	2	737	185	3
25	Kevin De Bruyne K. De Bruyne	23		77	5,896	67	0.30	19	42	2