Interseeding alfalfa (Medicago sativa L.) into native grasslands can enrich forage nutritive value, but successful establishment in semiarid regions is limited by chronic water deficit. The objective was to evaluate establishment and stand development of two upright-type alfalfa cultivars, ‘WL 440HQ’ (WL), ‘NuMex Bill Melton’ (NM), and prostrate-type ‘Falcata’– ‘Rhizoma’ blend (FR), interseeded into mixtures of four native grass species at 36-or 71-cm row spacing near Lubbock, TX. Average emergence was 265, 216, and 175 seedlings m−2 for WL, NM, and FR, respectively; however, the WL stand declined faster than the FR and NM stands during seedling and crown development stages (P < 0.01). The upright-type cultivars maintained a greater crown density and ground cover compared with FR at both row spacings (P < 0.05). Alfalfa seedling or crown density fitted against time (d) with exponential models revealed an initial sharp decline followed by a slow rate of decline after establishment. At the end of 3 yr, row-spacing results converged to similar levels for plant density (6.5 crowns m−2) and alfalfa cover (23.5%). This indicates significant seed cost savings with the wider row spacing at that level of stand establishment. Interseeding adapted, upright-type cultivars at wide row spacing can produce a desirable level of alfalfa establishment in a semiarid grassland of the southern Great Plains.