The study aimed to analyse the impact of silage from modified corn wet distillers’ grains plus solubles (WDGS) in dairy cow diets on milk production, composition, animal health and economic performance. The modified WDGS were prepared as a mixture of wet distillers’ grains (WDG), non-normative corn fraction (NNCF) and condensed corn distillers solubles (CCDS) in a ratio of 61:32:7 on a dry matter (DM) basis. Thirty dairy cows were divided into 3 groups (n = 10): a control group fed grass silage, corn silage, and concentrates; group W1 with 30% of corn silage DM replaced by WDGS silage; and group W2 with 65% DM replacement. Milk production, composition, and blood parameters were measured at baseline, and after 30 and 60 days. Cost and profitability analyses were also carried out. The highest milk production was recorded in group W2, while the lowest in the control group (P ≤ 0.01) during all measurements. On day 60, group W1 showed the highest content of polyunsaturated fatty acids (PUFA) (P ≤ 0.01), including ω-6 (P ≤ 0.05), while group W2 had the highest ω-3 content (P ≤ 0.05). Meanwhile, the highest concentration of plasma non-esterified fatty acids (NEFA) (P ≤ 0.05), γ-glutamyltransferase (γ-GT) activity (P ≤ 0.05) and malondialdehyde (MDA) content was determined in the control group (P ≤ 0.01). Modified corn WDGS silage is a valuable feed that can replace corn silage, reduce the need for protein components in dairy cow diets, and improve the profitability of milk production.