In several studies, the discriminating factor in land use of arable soil is tilling, along with its depth and intensity. Reduced and no-till technologies are held to be beneficial for soil health. Strip-till reduces soil disruption and enables the application of liquid fertilizer directly in rows at different levels. The objective of the research reported here was to evaluate the effects of digestate application on the biochemical and microbiological properties of soil at various soil depths. Three doses of digestate (0, 20, and 40 m3∙ha−1) applied at three different soil depths (0–10, 10–15, and 15–20 cm) were tested in two seasons (2020 and 2021) of semi-operational field trials with maize cultivated according to strip-till practice. In 2020, a lower (20 m3∙ha−1) dose of digestate caused the most significant improvement in β-glucosidase, urease, and basal and L-alanine-induced respiration in topsoil (0–10 cm) and in oxidizable carbon in mid-soil (10–15 cm). In 2021, the most significant positive effect on arylsulfatase, N-acetyl-β-D-glucosaminidase, urease, and all types of respiration were caused by higher (40 m3∙ha−1) digestate dose in mid-soil (10–15 cm). The benefits of the strip-till amended digestate in 2020, as revealed by respiration indicators, strongly decreased with soil depth. Finally, the markedly positive impacts of the digestate applied via the strip-till agromanagement technique were similar for three different depths of soil in 2021, verifying its benefits.